ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.2104C>T (p.Arg702Trp)

gnomAD frequency: 0.00001  dbSNP: rs528779319
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV004017433 SCV000205664 uncertain significance Rare genetic deafness 2022-12-01 criteria provided, single submitter clinical testing The p.Arg702Trp variant in CDH23 has been previously reported in one individual with autosomal recessive nonsyndromic hearing loss who carried causative variants in another gene (LMM unpublished data), and has been identified in 0.002% (1/41436) African/African American chromosomes by gnomAD (http://gnomad.broadinstitute.org, v3.1.2). However, this frequency is low enough to be consistent with a recessive allele frequency. This variant has also been reported in ClinVar (Variation ID 179166). Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2_Supporting.
GeneDx RCV001731486 SCV001982132 uncertain significance not provided 2021-10-04 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001731486 SCV003513526 uncertain significance not provided 2021-10-22 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 702 of the CDH23 protein (p.Arg702Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs528779319, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with CDH23-related conditions. ClinVar contains an entry for this variant (Variation ID: 179166). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C65"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Natera, Inc. RCV001275934 SCV001461614 uncertain significance Usher syndrome type 1 2020-04-15 no assertion criteria provided clinical testing

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